Diuretics

Question 1

Thiazide and related diuretics

Answer 1

Hydrochlorothiazide
Chlorthalidone
Indapamide
Metolazone

Question 2

Thiazide and related diuretics - MoA

Answer 2

Acts on early portion of the distal tubule to inhibit the Na+, Cl- symporter that participates in the reabsorption of sodium and chloride from this segment of the nephron. This action leads to the delivery of a greater volume of sodium and chloride-enriched tubular fluid to the late distal tubule and collecting duct, which in turn stimulates the exchange of sodium and potassium at these sites. In this process a small amount of potassium is secreted into urine in the tubules –> kaliuretic effect; can cause hypokalemia. Thiazide also increase magnesium excretion, but decrease calcium excretion in the urine.
Decrease Ca excretion result from decreased expression of Ca transport proteins (epithelial Ca channel calbindin, sodium-calcium exchanger protein) in renal tubules after thiazide adm.

Question 3

Thiazide and related diuretic - Clinical use

Answer 3

Hypertension
Edema associated with heart failure, cirrhosis, corticosteroid therapy, estrogen therapy.
Renal disorders such as nephrotic syndrome
Nephrogenic diabetes insipidus (decrease excessive urine V dramatically, reduction in plasma V –> increase Na&water reabsorption from proximal tubule –> less water delivered to diluting segments of nephron)
Nephrolithiasis (kidney stones) –> reduces Ca excretion

Question 4

Thiazide and related diuretic - Adverse effects

Answer 4

Hypokalemia –> hypokalemic metabolic alkalosis
Hyponatermia
Hypomagnesemia
Hyperglycemia
Hyperlipidemia
Hyperuricemia –> can lead to gout
Hypercalcemia
Decreases the insulin sensitivity –> can cause diabetes in some pat.
Thiazide-induced hypokalemia can decrease insulin secretion.
Blood cell deficiencies

Question 5

Thiazide and related diuretic - Interactions and Contraindication

Answer 5

Interactions:
Potentiated the diuretic effect of loop diuretics

Contraindications:
Hypotension
Sulfa-allergy
Gout
Renal failure
Lithium therapy
Hypokalemia
May worsen diabetes

Question 6

Which is the most frequently used thiazide diuretic?

Answer 6

Hydrochlorothiazide

Question 7

Loop diuretics

Answer 7

Furosemide
Bumetanide
Torsemide
Ethacrynic acid

Question 8

Loop diuretics - MoA

Answer 8

Inhibit the Na+, K+, 2Cl- symporter in the ascending limb of loop of Henle and thereby exert a powerful natriuretic effect. Inhibit the reabsorption of a greater percentage of filtered sodium and produce a dose dependent diuresis throughout their clinical dosage range.
They produce kaliuresis by increasing the exchange of sodium and potassium in the late distal tubule and collecting duct.
They increase magnesium and calcium excretion by reducing the reabsorption of these ions in the ascending limb by way of inh Na+K+2Cl- symporter. They cause a reduction of potassium back diffusion, and this increases magnesium and calcium excretion.

Question 9

Loop diuretics - Clinical use

Answer 9

Pulmonary edema(iv)
Preferred diuretics in the treatment of persons with renal impairment (creatinine clearance <30mL/min)
Edema caused by heart failure, cirrhosis.
Hypertension(but thiazide drugs are more preferred)
Hypercalcemia

Question 10

Loop diuretics - Adverse effects

Answer 10

Hypokalemia --> metabolic alkalosis
Hypocalcemia
hypomagnesemia
Hyponatremia
Hyperuricemia
Hyperglycemia
Hyperlipidemia
Ototoxicity; tinnitus, ear pain, vertigo and hearing deficits.
Blood cell deficiencies 
Hypersensitivity reactions

Question 11

Loop diuretics - Interactions

Answer 11

Diuretic effect decreased by NSAIDs. Adm with ACE inh may cause excessive hypotension

Question 12

Which loop diuretic has the highest incidence of ototoxicity?

Answer 12

Ethacrynic acid

Question 13

Potassium-Sparing Diuretics

Answer 13

Amiloride
Triamterene
Spironolactone
Eplerenone

Question 14

Potassium-Sparing Diuretics - Interactions

Answer 14

Adm with ACE inh or potassium –> hyperkalemia

Adm with NSAIDs –> renal failure

Question 15

Amiloride - MoA

Answer 15

Blocking the entry of sodium into the principal tubular cells of the late distal tubule and collecting duct, these drugs prevent sodium reabsorption at this site and indirectly reduce the secretion of potassium into the tubular filtrate and urine. They produce a modest amount of natriuresis but decrease kaliuresis.

Question 16

Amiloride - Clinical use

Answer 16

Treat hypokalemia induced by thiazide and loop diuretics

Question 17

Amiloride - Adverse effects

Answer 17

Hyperkalemia
Blood cell deficiencies
GI distress

Question 18

Spironolactone - MoA

Answer 18

Block aldosterone binding to the mineralocorticoid receptor in epithelial cells of the late distal tubule and collecting duct. When activated they interact with DNA to promote expression of genes for sodium channels and the sodium pump that enable sodium reabsorption and potassium secretion.
Reduces sodium reabsorption and accompanies secretion of potassium

Question 19

Spironolactone - Clinical use

Answer 19

Hyperaldosteronism
Reduce mortality in pat with heart failure
Prevent hypokalemia
Polycystic ovary disease and hirsutism (becayse of antiandrogenic effect)

Question 20

Spironolactone - Adverse effects

Answer 20

Gynecomastia
Impotence in men
Hyperkalemia

Question 21

Eplerenone - Clinical use

Answer 21

Counteract the effects of excessive aldosterone in pt with heart failure

Question 22

Osmotic Diuretics

Answer 22

Glycerol

Mannitol

Question 23

Osmotic Diuretics - MoA

Answer 23

Increased osmotic pressure of the plasma –> attract water from interstitial and transcellular fluids
decreased intraocular V & pressure by attracting water from ocular fluids into the circulation

Question 24

Osmotic Diuretics - Adverse effects

Answer 24

Excessive plasma V expansion –> heart failure and pulmonary congestion and edema
Nausea
Vomiting

Question 25

Osmotic Diuretics - Interactions

Answer 25

Potentiates effects of other diuretics

Question 26

Glycerol - Clinical use

Answer 26

Acute glaucoma

Question 27

Mannitol - MoA

Answer 27

After IV adm, it is filteres at the glomerulus but not reabsorbed from the renal tubules. Osmotically attracts and retains water as it moves through the nephron and into the urine --> decreased tubular sodium conc and conc gradient between tubular fluid and cells --> retards the reabsorption of sodium

Question 28

Mannitol - Clinical use

Answer 28

Cerebral edema and reduce intracranial pressure Acute glaucoma Diuretic --> improve renal function in the oliguric phase of acute renal failure Maintain renal function and decreased renal toxicity of antineoplastic platinum compounds (cisplatin) Promote renal excretion of toxic substances in cases of drug overdose or poisoning.

Question 29

Carbonic Anhydrase Inhibitors

Answer 29

Acetazolamide | Dorzolamide

Question 30

Carbonic Anhydrase Inhibitors - MoA

Answer 30

Inh CA throughout the body. This enzyme catalyzes the conversion of CO2 and water to carbonic acid which spontaneously decomposes to bicarbonate and hydrogen ions. CA catalyzes the formation of bicarbonates and participates in this way in aqueous humor formation; bicarbonate is secreted into the posterior chamber of the eye along with water and other substances that make up the aqueous humor secretion and intraocular pressure. CA is required for the reabsorption of sodium bicarbonate from the prox tubule and for secretion of hydrogen ions in the collecting duct. In the reabsorption of sodium bicarbonate, bicarbonate must be converted to CO2 and water by CA, because apical cell membrane of tubular epithelial cells is impermeable to bicarbonate. CO2 and water can diffuse into the tubular cells, where CA converts them back into bicarbonate --> transported into the interstitial fluid for diffusion into the circulation. Inh of this --> decrease reabsorption of sodium bicarbonate and increase in its renal excretion --> alkalinization of urine --> hyperchloremic metabolic acidosis. Hyperchloremia due to increased reabsorption of chloride as a compensation for decreased bicarbonate reabsorption. Counteract fluid retention --> decrease in CSF pressure + prevent fall in CSF pH. Inhibition in CNS: increase seizure threshold

Question 31

Carbonic Anhydrase Inhibitors - Clinical use

Answer 31

Glaucoma (acute&chronic) Used to alkalinize the urine Prevention and treatment of high-altitude sickness (mountain sickness) (counteract respiratory alkalosis) Epilepsy

Question 32

Carbonic Anhydrase Inhibitors - Adverse effects

Answer 32

``` Drowsiness Paresthesia Hypokalemia Hyperglycemia Hypersensitivity Blood cell deficiencies Hepatic insufficiency Metabolic acidosis Uremia ```

Question 33

Carbonic Anhydrase Inhibitors - Interactions

Answer 33

Decrease excretion of weak bases (amphetamine, pseudoephedrine, quinidine) --> increased serum levels and cause toxicity Serum levels increased by salicylates

Question 34

Dorzolamide - Clinical use

Answer 34

Glaucoma | Ocular hypertension

Question 35

Dorzolamide - Adverse effects

Answer 35

Bitter taste Blurred vision Ocular discomfort Allergic reactions

Question 36

Antidiuretic Hormone Antagonist

Answer 36

Conivaptan | Tolvaptan

Question 37

Antidiuretic Hormone Antagonist - MoA

Answer 37

V2: coupled with insertion of aquaporin channels in the apical membranes of renal collecting ducts --> reabsorption of water. --> Help maintain plasma osmolality Antagonism of V2: free water excretion --> aquaresis

Question 38

Antidiuretic Hormone Antagonist - Clinical use

Answer 38

Euvolemic and hypervolemic hyponatremia

Question 39

Antidiuretic Hormone Antagonist - Adverse effects

Answer 39

Hypernatremia

Question 40

Antidiuretic Hormone Antagonist - Contraindications

Answer 40

hypovolemic hyponatremia | Pt taking 3A4 inhibitors

Question 41

Antidiuretic Hormone Antagonist - Interactions

Answer 41

Increase serum levels of midazolam, simvastatin + drugs metabolized by 3A4.

Question 42

Conivaptan - MoA

Answer 42

Blocks V1A and V2 receptors

Question 43

Tolvaptan - MoA

Answer 43

Blocks V2 receptors